Functional genomics study funded

Published May 17, 2004; Category: DARTMOUTH MEDICAL SCHOOL

DMS awarded $9 million from NIH

The department of genetics at Dartmouth Medical School has received a $9 million National Institutes of Health grant to lead a collaboration in functional genomics that will be one of the most comprehensive to date within the group of organisms studied. The grant from National Institute of General Medical Sciences will be used primarily to analyze the roles and functions of genes in filamentous fungi that could shape future medical studies, including the development of antibiotics and treatments.

"We're truly excited about this project, and the fact that it will be centered at Dartmouth Medical School," said Jay Dunlap and Jennifer Loros, both Professors of Genetics and Biochemistry at Dartmouth Medical School (DMS) who will lead two of the four collaborative projects. Other institutions listed in the grant include UC Berkeley, UCLA, MIT, University of New Mexico, University of Missouri and Oregon Health Sciences University.

"Filamentous fungi, for which Neurospora is perhaps the best understood model organism, have major significance on the planet," said Dunlap. "They include a number of significant animal, human and plant pathogens, as well as a large number of strains used in industrial manufacture. This study will provide a foundation for a great deal of further work."

Neurospora crassa, better known as bread mold, is an important model in genetics research, although it has yet to be fully investigated. Fungi allied to Neurospora include several pathogens and have been manipulated to produce antibiotics and pharmaceuticals. While about 60 percent of the genes in Neurospora enable functions shared by other organisms including people, about 40 percent of the more than 10,000 genes in Neurospora are apparently novel and activate biochemical functions that will be new, suggesting that examination of the functions of these genes will be informative.

"Neurospora is a fascinating fungus," said DMS Dean Stephen P. Spielberg. "It is an enormously helpful model system; organisms like it cause disease, manufacture medicine and most biomass turnover on the planet requires filamentous fungi. This grant represents a wealth of promising research opportunities and we look forward to understanding the gene expression of this potentially groundbreaking genetic model. The results of this study will probably change our thinking about how we look at humans and gene expression."

The bread mold fungus has been central to the field of genetics for decades. George Beadle and Edward Tatum won the Nobel prize in 1958 for discovering, through their work on Neurospora, that genes act by regulating chemical events. Since then, the Neurospora genome has been fully sequenced and is predicted to have 10,082 proteins, but it has not been the subject of intense analysis of this magnitude until now.

The five-year grant among the institutions will be spent on four interconnected projects aimed at shedding light on Neurospora's potentially wide range of genomic functions.

The research projects, whose results will be available to the public, will:

Pursue the systematic disruption of genes through targeted gene replacements;

Produce a platform for electronically capturing community feedback and data about the existing annotation;

Provide a baseline analysis of gene expression under a variety of growth conditions and;

Generate cDNA libraries and a Single Nucleotide Polymorphism map from wild type and related strains.